Investigational agents for treatment of AIDS-related Kaposi’s sarcoma

Abstract

AIDS-related Kaposi’s sarcoma (KS) is a neoplasm that results from the co-infection of HIV and KS herpesvirus/human herpesvirus-8 (KSHV/HHV8). Targeting HIV with highly active antiretroviral therapy has attenuated the natural history of this disease. Recent discoveries have elucidated the role of multiple signaling pathways in the pathogenesis of AIDS-related KS. In particular, KSHV/HHV8-specific gene products, including a G-protein-coupled receptor (vGPCR) and a homolog of human IL-6 (vIL-6), have been implicated in the development of tumorigenesis and angiogenesis. In addition, KSHV/HHV8 can modulate cellular growth and angiogenic pathways to augment malignant transformation and potentiate growth. This article discusses the main signaling pathways that are implicated in the pathogenesis of AIDS-related KS, reviews recently completed clinical trials and anticipates the future direction of molecularly targeted agents in this disease.

Keywords::

• angiogenesis inhibitors
• fumagillin
• human herpesvirus-8
• imatinib
• IL-12 Kaposi’s sarcoma
• Kaposi’s sarcoma-associated herpesvirus
• matrix metalloprotease
• rapamycin
• thalidomide

Acknowledgements

The authors thank HB Koon, MD for critical review of this manuscript, and are grateful to J Bell and J Hayward of Media Services for assistance with Figure 1.

Notes

*Targets for which inhibitors have been tested or are being tested as therapy against KS. bFGF: Basic fibroblast growth factor; HHV: Human herpesvirus; HIF: Hypoxia-inducible factor; IGF: Insulin-like growth factor; KS: Kaposi’s sarcoma; KSHV: KS herpesvirus; MMP: Matrix metalloprotease; PDGF: Platelet-derived growth factor; SCF: Stem cell factor; vCCl: Viral CC-class chemokine; VEGF: Vascular endothelial growth factor; vGPCR: A G-protein-coupled receptor encoded by KSHV; vIL: Viral IL encoded by KSHV.